Resuscitation outcomes in patients with cancer: experience in a large urban cancer centre.

PURPOSE: Hospitalized patients with cancer who experience cardiopulmonary arrest have historically low survival rates. This retrospective cohort study describes outcomes of patients at a large Canadian cancer centre who had a "code medical emergency" activated, and the use of pragmatic criteria to identify patients with poor survival following resuscitation. METHODS: We included hospitalized patients with cancer who had a "code blue" activated between January 2007 and December 2018. Our primary outcome was intensive care unit (ICU) mortality. We developed pragmatic criteria to identify patients with "poor prognosis" for survival from cardiopulmonary resuscitation (CPR) based on disease status and candidacy for further cancer treatment. We used descriptive statistics to analyze the outcomes of poor prognosis patients. RESULTS: Two hundred and twenty-five patients had a code blue activated. The median age was 61 yr, 52% were male, and 48% had a solid tumour. Overall, 173/225 (77%) patients survived the code blue; 164 were admitted to the ICU, where 49% (81/164) died; 31% survived to hospital discharge; and 16% (n = 27) were alive at one year. One hundred and twenty out of 225 (53%) required chest compressions; spontaneous circulation returned in 61% (73/120), and 12% (14/120) survived to hospital discharge. Patients meeting "poor prognosis" criteria (114, 51%) were more likely to die in the ICU (64% vs 35%; P < 0.001) or in hospital (86% vs 59%; P < 0.001), and more often had goals-of-care discussions prior to the code blue (46% vs 7%; P < 0.001). At one year, only 2% of poor prognosis patients were alive, compared with 24% of patients who did not meet any poor prognosis criteria. CONCLUSION: Hospitalized patients with cancer requiring CPR have poor hospital and long-term outcomes. The proposed set of pragmatic criteria may be useful to identify patients unlikely to benefit from CPR and life support, to trigger early goals of care discussions, and to avoid potentially goal-discordant interventions.

RéSUMé: OBJECTIF: Les patient·es hospitalisé·es atteint·es d'un cancer qui subissent un arrêt cardiorespiratoire ont des taux de survie historiquement bas. Cette étude de cohorte rétrospective décrit les issues des patient·es d'un grand centre canadien de cancérologie pour qui un « code d'urgence médicale ¼ a été activé et l'utilisation de critères pragmatiques pour identifier les patient·es ayant une faible survie après réanimation. MéTHODE: Nous avons inclus les personnes hospitalisées atteintes d'un cancer pour qui un « code bleu ¼ avait été activé entre janvier 2007 et décembre 2018. Notre critère d'évaluation principal était la mortalité à l'unité de soins intensifs (USI). Nous avons développé des critères pragmatiques pour identifier les personnes ayant un « mauvais pronostic ¼ de survie à la réanimation cardiorespiratoire (RCR) en fonction de l'état de la maladie et de leur éligibilité à un traitement ultérieur contre le cancer. Nous avons utilisé des statistiques descriptives pour analyser les issues des patient·es ayant un mauvais pronostic. RéSULTATS: Un code bleu a été activé pour deux cent vingt-cinq patient·es. L'âge médian était de 61 ans, 52 % étaient des hommes et 48 % avaient une tumeur solide. Dans l'ensemble, 173/225 (77 %) patient·es ont survécu au code bleu; 164 ont été admis·es aux soins intensifs, où 49 % (81/164) sont décédé·es; 31 % ont survécu jusqu'à leur congé de l'hôpital; et 16 % (n = 27) étaient en vie après un an. Cent vingt sur 225 (53 %) ont nécessité des compressions thoraciques; la circulation spontanée est revenue chez 61 % (73/120), et 12 % (14/120) ont survécu jusqu'à leur congé de l'hôpital. Les patient·es répondant aux critères de « mauvais pronostic ¼ (114, 51 %) étaient plus susceptibles de mourir à l'USI (64 % vs 35 %; P < 0,001) ou à l'hôpital (86 % vs 59 %; P < 0,001) et avaient plus souvent eu des discussions sur les objectifs de soins avant l'activation du code bleu (46 % vs 7 %; P < 0,001). À un an, seulement 2 % des patient·es ayant un mauvais pronostic étaient en vie, contre 24 % des patient·es qui ne présentaient aucun critère de mauvais pronostic. CONCLUSION: Les personnes hospitalisées atteintes d'un cancer nécessitant une RCR ont de mauvaises issues intra-hospitalières et à plus long terme. L'ensemble de critères pragmatiques proposé peut être utile pour identifier la patientèle peu susceptible de bénéficier de la RCR et du maintien des fonctions vitales, pour amorcer rapidement des discussions sur les objectifs de soins et pour éviter les interventions potentiellement discordantes par rapport à ces objectifs.

Why We Swab: A library of stories in stem cell donation.

BACKGROUND: Stories are powerful in their ability to disseminate information in a meaningful way. We hypothesized that a stem cell donation story library optimized for social media could support the education and recruitment of committed unrelated hematopoietic stem cell donors from needed demographic groups. STUDY DESIGN AND METHODS: We developed Why We Swab, a library of stories on stem cell donation (facebook.com/WhyWeSwab; instagram.com/WhyWeSwab; twitter.com/WhyWeSwab), and evaluated its impact across social and traditional media as well as on eligible potential donors' knowledge and attitudes towards donation. RESULTS: As of December 2021, the library included 28 story arcs featuring 45 storytellers from diverse ancestral backgrounds, including 8 donor-recipient stories. Overall, the stories reached >92,000 people across social media. Notably, stories were republished by 18 print/ broadcast media outlets in Canada and by major medical organizations. A series of stories shown to 33 eligible potential donors improved mean total scores on a donation knowledge test (64% to 85%, p < 0.001), reduced mean ambivalence scale scores (3.85 to 2.70, p < 0.001), and improved participants' willingness to register as donors (45% to 73%, p < 0.005). Data are also shown demonstrating that stakeholders valued the library and that its deployment was associated with improved donor recruitment outcomes in Canada. CONCLUSION: Why We Swab is accessible and relevant to a wide audience, including stem cell donor registries and recruitment organizations seeking to improve their recruitment efforts as well as to blood and organ & tissue donation organizations who can adapt the Why We Swab model to their audiences.

Catheter management across patients with hematologic malignancies and catheter-related blood stream infections: a systematic review.

Catheter-related bloodstream infection (CRBSI) can lead to ICU admission in patients with hematologic malignancy (HM). Variability exists in the management of catheters given the need for long-term access and co-existing thrombocytopenia or coagulopathy. We conducted a systematic review to evaluate catheter management in patients with CRBSI. Literature searches were conducted up to December 20, 2021 across MEDLINE, EMBASE, CENTRAL, CINAHL, and PubMed. Observational studies and RCTs of adults (> 16) with HM were included. Our primary outcome was mortality and secondary outcomes included infection recurrence and ICU admission. We identified 23 studies (N = 2026 patients), of which 22 were observational. Across the 12 studies (N = 801) that reported on bacterial organisms, 528 (65.9%) were gram positive, and 273 (34.1%) were gram negative. Catheters were removed in 1266 (62%) and retained in 760 (38%) patients. Removal was associated with a mean 30-day mortality of 13.14% (SD 9.12; 90/685) and reinfection rate of 5.49% (SD 2.88; 22/401) compared to 39.23% (SD 14.58; 122/311) and 10.75% (SD 21.07; 10/93), respectively, if retained. Catheter retention may be associated with a higher risk of mortality and infection recurrence. Further prospective research should assess catheter management in this population, including potential harms associated with retention.

Safety of two-hour intermittent intravenous infusions of tacrolimus in the allogeneic hematopoietic stem cell transplantation unit.

At our institution, tacrolimus is used as a second-line agent for the prevention and treatment of graft-versus-host-disease in the allogeneic hematopoietic stem cell transplantation (HSCT) unit after patients have experienced a serious or intolerable adverse event to cyclosporine. As per our standard practice, tacrolimus is administered via 2-h intermittent IV infusions (IIVs) every 12 h rather than continuous IV infusion. Shorter infusion times are cautioned due to concerns of higher rates of nephrotoxicity, neurotoxicity and infusion-related reactions, although there is a paucity of data to support this claim. Our primary objective was to evaluate the safety of a 2-h IIV of tacrolimus in an adult HSCT population. We retrospectively reviewed the charts of 104 patients who received tacrolimus by IIV (3574 doses; median = 22, range 1-158, IQR = 28) from 2002 to 2016. Primary outcomes collected include rates of nephrotoxicity, neurotoxicity and infusion-related reactions. One (0.9%) grade 2 infusion-related reaction occurred and resolved without discontinuation of tacrolimus. Of 16 incidences (13.6%) of nephrotoxicity, all but 10 (8.5%) cases resolved. Precipitating factors for nephrotoxicity unrelated to tacrolimus were identified in all 10 cases. There were 41 incidences (35%) of neurotoxicity, of which, 8 (6.8%) were considered serious. All neurotoxicity reverted to baseline or resolved completely. We propose that a 2-h IIV of tacrolimus is a safe method of administration in the adult HSCT setting.

Influence of FLT3-ITD and NPM1 status on allogeneic hematopoietic cell transplant outcomes in patients with cytogenetically normal AML.

OBJECTIVE: In individuals with cytogenetically normal (CN) AML, disease risk is estimated using molecular features such as the status of NPM1 and FLT3-ITD genes. However, data regarding the impact of NPM1 and FLT3-ITD status on hematopoietic stem cell transplant (HCT) outcomes are limited. We examined the effect of NPM1 and FLT3-ITD status on transplant outcomes in 131 CN AML patients transplanted at Princess Margaret Hospital between 2006 and 2017. METHODS: Overall survival (OS) was calculated using Kaplan-Meier analysis and multivariable Cox proportional hazards regression. Cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were calculated using competing risk regression. RESULTS: There was no difference in 3-year OS among NPM1+ /FLT3-ITD- , NPM1- /FLT3-ITD- , NPM1+ /FLT3-ITD+ and NPM1- /FLT3-ITD+ patients: 56% (95% CI, 29%-76%), 61% (95% CI, 46%-73%), 53% (95% CI, 34%-70%) and 52% (95% CI, 17%-78%), respectively. CIR at 3-years was similar among NPM1- /FLT3-ITD- , NPM1+ /FLT3-ITD+ and NPM1- /FLT3-ITD+ patients-14% (95% CI, 6%-26%), 13% (95% CI, 4%-28%) and 19% (95% CI, 4%-41%), respectively-while there were no relapses in the NPM1+ /FLT3-ITD- group. NRM at 3 years for NPM1+ /FLT3-ITD- , NPM1- /FLT3-ITD- , NPM1+ /FLT3-ITD+ and NPM1- /FLT3-ITD+ patients was similar at 44% (95% CI, 19%-67%), 38% (95% CI, 25%-50%), 43% (95% CI, 25%-59%) and 44% (95% CI, 14%-71%), respectively. CONCLUSION: NPM1 and FLT3-ITD status may provide limited prognostic information about transplant outcomes in CN AML patients.

Low rates of acute and chronic GVHD with ATG and PTCy in matched and mismatched unrelated donor peripheral blood stem cell transplants.

INTRODUCTION: We evaluated the combination of ATG and PTCy for GVHD prophylaxis in matched and mismatched unrelated PBSCTs for high-risk hematological malignancies. METHODS: We treated 102 patients with reduced intensity conditioning (RIC) with fludarabine, busulfan, and TBI 200 cGy. GVHD prophylaxis included rabbit ATG (thymoglobulin at total dose of 4.5 mg/kg divided over days -3 to -1), PTCy (50 mg/kg/day on day +3 and on day +4), and cyclosporine. Clinical and outcome data were collected retrospectively. RESULTS: Among 102 patients, 76 patients received 10/10 MUD transplants and 26 patients received 9/10 mismatched transplants. The median age was 59 years. At a median follow-up of 15 months (range 0.6 to -33 months), the 1-year OS in MUD and MMUD cohort was 75% and 50%, respectively (P = 0.027). The corresponding one-year PFS was 67% and 35%, respectively (P = 0.0024). The incidence of grade 3-4 acute GVHD was 11.8% in MUD and 3.8% in MMUD group, and that of NIH stage moderate/severe chronic GVHD in the 2 groups was 10.5% and 7.6%, respectively. Cytomegalovirus (CMV) reactivation was seen in 49% patients. The cumulative incidence of relapse was 21.1% in the MUD group and 42.3% in the MMUD group. CONCLUSION: Our experience shows that PTCy and ATG can be combined for GVHD prophylaxis in matched unrelated donor PBSCTs with low rates of Gr3-4 acute GVHD and chronic GVHD, and acceptable relapse rates.

Reduced-Intensity Conditioning and Dual T Lymphocyte Suppression with Antithymocyte Globulin and Post-Transplant Cyclophosphamide as Graft-versus-Host Disease Prophylaxis in Haploidentical Hematopoietic Stem Cell Transplants for Hematological Malignancies.

Haploidentical hematopoietic stem cell transplantation (haploHSCT) with conditioning regimens using post-transplant cyclophosphamide (PTCy) for peripheral blood stem cell (PBSC) grafts is limited by comparably higher rates of acute and chronic graft-versus-host disease (GVHD). Antithymocyte globulin (ATG) may mitigate this risk. We evaluated haploHSCT after reduced-intensity conditioning (RIC) with ATG, PTCy, and cyclosporine to prevent rejection and GVHD. Fifty adults underwent haploHSCT from August 2016 to February 2018. RIC included fludarabine (30 mg/m2/day on days -5 to -2), busulfan (3.2 mg/m2/day on days -3 and -2), and total body irradiation (200 cGy) on day -1. Unmanipulated PBSCs were infused on day 0. GVHD prophylaxis included ATG (4.5 mg/kg over days -3 to -1), PTCy (50 mg/kg/day on days +3 and +4), and cyclosporine from day +5. Median age was 56 years (range, 22 to 70 years); 25 (73.5%) patients were in first complete remission (CR1), 5 (14.7%) were in second complete remission (CR2), and 8 (23.5%) had active disease. Median time to neutrophil engraftment was 16 days (range, 8 to 43 days). At day +100, the cumulative incidence of acute GVHD of any grade, and grades III to IV was 38.3% and 5.2%, respectively. Mild chronic GVHD was seen in 15.5%. Cytomegalovirus (CMV) reactivation occurred in 37 (74%) cases and CMV disease occurred in 4 (11.5%) cases. Epstein-Barr virus (EBV) reactivation occurred in 21 (61.8%) patients. The incidence of histologically confirmed post-transplantation lymphoproliferative disorder (PTLD) was 5.8%. Four patients received rituximab. There were no CMV, EBV, or PTLD-related deaths. Six-month and 1-year overall survival (OS), cumulative incidence of relapse (CIR), and nonrelapse mortality (NRM) were 73.9%, 10.2%, and 19.4%, respectively, and 48.1%, 16% and 38.2%, respectively. Infection was the most common cause of death (18%). Unmanipulated haploidentical PBSC transplantation following RIC with ATG, PTCy, and cyclosporine as a GVHD prevention strategy results in low rates of acute and chronic GVHD.

Incidence and Risk Factors for Nontuberculous Mycobacterial Infection after Allogeneic Hematopoietic Cell Transplantation.

Allogenic hematopoietic stem cell transplant (HCT) recipients are at risk of many infections. Nontuberculous mycobacteria (NTM) are increasingly recognized as clinically significant pathogens in this population. We investigated the incidence and risk factors for NTM infection after allogeneic HCT. This retrospective cohort study included all patients with allogeneic HCT at our institution during 2001 to 2013. Patients who developed significant NTM infection (NTM disease) were identified. Multivariable modeling was used to identify risk factors for NTM disease, and a risk score model was constructed to identify high-risk patients. Of 1097 allogeneic HCT patients, 45 (4.1%) had NTM isolated and 30 (2.7%) had NTM disease (28 [93.3%] exclusively pulmonary, 2 [6.7%] pulmonary plus another site). Incidence of NTM infection by competing risk analysis was 2.8% at 5 years (95% CI, 1.9% to 4.0%). The median time to diagnosis was 343 days (range, 19 to 1967). In Fine-Gray proportional hazards modeling, only global severity of chronic graft-versus-host disease (cGVHD) (HR, 1.99; 95% CI, 1.12 to 3.53; P = .019,) and cytomegalovirus (CMV) viremia (HR, 5.77; 95% CI, 1.71 to 19.45; P = .004) were significantly associated with NTM disease. Using these variables a risk score was calculated: 1 point for CMV viremia or moderate cGVHD and 2 points for severe cGVHD. The score divided patients into low risk (0 to 1 points, n = 820 [77.3%], 3-year NTM risk 1.2%), intermediate risk (2 points, n = 161 [15.4%], 3-year NTM risk 7.1%), and high risk (3 points, n = 56 [5.4%], 3-year NTM risk 14.3%). NTM disease after allogeneic HCT is common. Severe cGVHD and CMV viremia are associated with increased risk, permitting risk stratification.

Efficacy of Cidofovir in Treatment of BK Virus-Induced Hemorrhagic Cystitis in Allogeneic Hematopoietic Cell Transplant Recipients.

BK virus-associated hemorrhagic cystitis (BK-HC) is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HCT), with incidences up to 70%. Cidofovir is an antiviral agent with growing evidence as a therapeutic intervention. To assess the safety profile and efficacy of intravenous and intravesical cidofovir in allo-HCT patients with BK-HC, a retrospective study was undertaken of the allo-HCT cohort who received cidofovir for symptomatic BK-HC (hematuria with BK viruria or viremia) from January 2010 until March 2017 in a single transplant center in Ontario, Canada. The primary outcome measure was a reduction in BK-HC severity (graded from 1 to 4); secondary outcomes included overall survival, BK virus titers, and the onset of acute kidney injury. Twelve allo-HCT patients received cidofovir for BK-HC, with pretreatment clinical severity of 3 (50%) or 4 (50%). Cidofovir was administered via intravenous (33%), intravesical (58%), or both modalities (8%). After a median cumulative dose of 10 mg/kg (range, 1 to 37), mean BK-HC grade decreased significantly by 1.8 (3.5 precidofovir, 1.7 postcidofovir, P < .01). Sixty-six percent of patients had at least partial response to cidofovir, with similar response rates between intravenous (66%) and intravesical (62%) administration. Sixty-seven percent of patients died, and 33% of patients experienced renal toxicity, including 2 patients receiving intravesical therapy. In this retrospective series, there was a significant reduction in BK-HC severity after cidofovir administration; most patients achieved at least partial response after cidofovir administration. Even with intravesical instillation, acute kidney injury remains a potential complication of cidofovir. Although cidofovir may be an efficacious therapy for BK-HC, albeit with potential demonstrated toxicities, further prospective trials are needed.

Fludarabine and busulfan plus low-dose TBI as reduced intensity conditioning in older patients undergoing allogeneic hematopoietic cell transplant for myeloid malignancies.

We have been using a combination of fludarabine/busulfan plus low-dose total body irradiation (TBI) as the reduced-intensity conditioning (RIC) regimen for patients age ≥ 60 years undergoing allogeneic hematopoietic cell transplantation (HCT) for myeloid malignancies. We retrospectively analyzed outcomes of 116 older patients (median age 64 years) who underwent HCT from 2006 to 2015 for myeloid malignancies, including acute myeloid leukemia (AML) in first complete remission (CR1). On univariate analysis, overall survival (OS) for the cohort at 3 years was 33% (95% CI 25-42). Cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) at 3 years were 24% (95% CI 16-32) and 43% (95% CI 34-52), respectively. Multivariable analysis for OS demonstrated AML patients to have superior outcome (HR 1.60 for other myeloid, 95% CI 1.01-2.54, p = 0.045), as well as related donors (HR 1.92 for unrelated, 95% CI 1.22-3.03, p = 0.005). For NRM, AML patients had superior outcome (HR 1.76 for other myeloid, 95% CI 1.03-3.01, p = 0.038), as well as patients with related donors (HR 1.81 for unrelated, 95% CI 1.07-3.07, p = 0.028). We then demonstrated that AML patients with related donors (n = 45) had superior 3-year OS of 51% (95% CI 36-65), compared to 21% (95% CI 12-32) for all other patients (p = 0.0003). We conclude that the RIC regimen used is effective for older patients, particularly AML patients in CR1 with matched related donors.

Outcome following second allogeneic hematopoietic cell transplantation: A single-center experience.

OBJECTIVE: Second allogeneic hematopoietic cell transplantation (HCT) may be indicated following relapse or graft failure following first HCT. Our retrospective single-center study sought to investigate parameters that influence post-second allogeneic HCT survival. METHOD: We investigated 92 patients who underwent second allogeneic HCT between 1980 and 2016 for relapse or graft failure following first HCT. Median age at second HCT was 41 years (range 16-68), performed for relapse in 59 patients (64%) and for graft failure in 33 patients (36%). RESULTS: On univariate analysis, 3-year OS of the entire cohort was 35% (95% CI=25-45). Eastern Cooperative Oncology Group (ECOG) score (3-year OS 48% for ECOG 0-1, 18% for ECOG 2-3, P=.0006), second HCT indication (3-year OS 43% for relapse, 20% for graft failure, P=.02), time from first HCT to relapse/graft failure (3-year OS for <12months 21%, for ≥12months 46%, P=.009), and conditioning intensity (3-year OS for MA 42% vs other regimens 23%, P=.08) significantly influenced OS. Multivariable analysis confirmed ECOG score (HR=2.15 for ECOG 2-3, 95% CI=1.32-3.51, P=.002) and second HCT indication (HR=1.67 for graft failure, 95% CI=1.02-2.75, P=.04) to independently influence survival. CONCLUSION: Second HCT may offer long-term survival particularly to patients with good performance status who relapse post-first HCT.

Prolonged granulocyte colony stimulating factor use in glycogen storage disease type 1b associated with acute myeloid leukemia and with shortened telomere length.

Glycogen storage disease (GSD) type 1 is a rare autosomal recessive inherited condition. The 1b subtype comprises the minority of cases, with an estimated prevalence of 1 in 500,000 children. Patients with glycogen storage disease type 1b are often treated with granulocyte colony stimulating factor (G-CSF) for prolonged periods to improve symptoms of inflammatory bowel disease (IBD) and in the face of severe neutropenia to decrease risk of infection. Long-term G-CSF treatment may result in an increased risk of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) possibly due to increased marrow stress resulting in telomere shortening. To our knowledge, there have been two published cases of AML in GSD type 1b patients following long-term G-CSF exposure. Here, we report two further cases of AML/MDS-related changes in patients GSD type 1b treated with G-CSF. One patient developed AML with complex karyotype after 20 years of G-CSF treatment. The second patient was found to have short telomeres after 10 years of G-CSF exposure, but no evidence of acute leukemia at present. The third patient developed AML/MDS after 25 years of G-CSF use, with short telomeres prior to bone marrow transplant. Together these cases suggest that GSD type 1b patients with prolonged G-CSF exposure may be at an increased risk of MDS/AML states associated with G-CSF-induced shortened telomeres. We recommend that any GSD1b patients with prolonged G-CSF should have routine telomere assessments with monitoring for MDS if telomere shortening is observed, and with particular attention warranted if there is unexplained loss of G-CSF responsiveness.

Extramedullary disease at diagnosis of AML does not influence outcome of patients undergoing allogeneic hematopoietic cell transplant in CR1.

OBJECTIVE: Extramedullary disease (EMD) at diagnosis of acute myeloid leukemia (AML) has been associated with increased risk of relapse and worse outcomes post-chemotherapy. This study sought to investigate the association of EMD with outcomes following allogeneic hematopoietic cell transplantation (allo-HCT). METHODS: This single-center retrospective study investigated the impact of EMD at diagnosis on the outcome of patients transplanted for AML in first complete remission (CR1). The study included 303 consecutive patients with AML transplanted in CR1, median age 51 years (range 18-71). RESULTS: EMD at diagnosis was documented in 39 patients (13%), either histologically (26 patients) or clinically/radiologically (13 patients). Among the 39 EMD patients, 16 had CNS disease, seven had gingival infiltration, and five had leukemia cutis. On univariate analysis, EMD had no significant impact on survival, with a 3-year OS of 55% (95% CI 38-69) compared to 48% for the non-EMD group (95% CI 42%-55%) (P=.84). Likewise, 3-year CIR was 18% vs 19% (P=.86) and 3-year NRM was 26% vs 33% (P=.83) for EMD vs non-EMD groups, respectively. Multivariate analysis confirmed these results. CONCLUSIONS: We conclude that EMD at diagnosis of AML does not seem to influence outcomes following allo-HCT performed in CR1.

Long-term survival and functional outcomes of critically ill patients with hematologic malignancies: a Canadian multicenter prospective study.

PURPOSE: Patients with hematologic malignancy (HM) commonly develop critical illness. Their long-term survival and functional outcomes have not been well described. METHODS: We conducted a prospective, observational study of HM patients admitted to seven Canadian intensive care units (ICUs) (2018-2020). We followed survivors at 7 days, 6 months and 12 months following ICU discharge. The primary outcome was 12-month survival. We evaluated functional outcomes at 6 and 12 months using the functional independent measure (FIM) and short form (SF)-36 as well as variables associated with 12-month survival. RESULTS: We enrolled 414 patients including 35% women. The median age was 61 (interquartile range, IQR: 52-69), median Sequential Organ Failure Assessment (SOFA) score was 9 (IQR: 6-12), and 22% had moderate-severe frailty (clinical frailty scale [CFS] ≥ 6). 51% had acute leukemia, 38% lymphoma/multiple myeloma, and 40% had received a hematopoietic stem cell transplant (HCT). The most common reasons for ICU admission were acute respiratory failure (50%) and sepsis (40%). Overall, 203 (49%) were alive 7 days post-ICU discharge (ICU survivors). Twelve-month survival of the entire cohort was 21% (43% across ICU survivors). The proportion of survivors with moderate-severe frailty was 42% (at 7 days), 14% (6 months), and 8% (12 months). Median FIM at 7 days was 80 (IQR: 50-109). Physical function, pain, social function, mental health, and emotional well-being were below age- and sex-matched population scores at 6 and 12 months. Frailty, allogeneic HCT, kidney injury, and cardiac complications during ICU were associated with lower 12- month survival. CONCLUSIONS: 49% of all HM patients were alive at 7 days post-ICU discharge, and 21% at 12 months. Survival varied based upon hematologic diagnosis and frailty status. Survivors had important functional disability and impairment in emotional, physical, and general well-being.

Treatment of Philadelphia chromosome-positive acute lymphoblastic leukaemia with imatinib combined with a paediatric-based protocol.

Although the combination of tyrosine kinase inhibitors with chemotherapy is widely used for young adults with Philadelphia chromosome positive-acute lymphoblastic leukaemia (Ph+ ALL), the outcome and safety of this combination using intensive paediatric-based protocols has not been well described. The clinical course of 32 adults age 18-60 years with Ph+ ALL treated with a paediatric-based protocol plus imatinib was evaluated. The complete response rate was 94%. Grade 3-4 infections, neuropathy, myopathy and liver function abnormalities were common, resulting in major treatment delays and dose reductions, and declines in performance status (physical deconditioning), particularly in patients aged 41-60 years. Median and 3-year overall survival (OS) was 40·7 months and 53%, respectively, and median and 3-year even-free survival (EFS) was 30·1 months and 50%, respectively. OS and EFS were inferior in deconditioned patients. Of 16 patients who underwent haematopoietic stem cell transplantation (HSCT) in first complete remission, six died of non-relapse complications. There was no significant difference in OS and EFS between transplanted and non-transplanted patients, based on an intention-to-treat and time-to-donor identification analysis. The combination of imatinib with a paediatric-based regimen in adults produced high response rates, but was associated with considerable toxicity and high non-relapse mortality post-HSCT.

Clinical diagnostic accuracy of respiratory failure in critically ill hematopoietic stem cell transplant patients.

RATIONALE: Acute respiratory failure (ARF) is a frequent complication following hematopoietic cell transplantation (HCT). We aimed to characterize the etiologies of ARF in patients who died in the intensive care unit following HCT based on autopsy findings. We then evaluated agreement between the clinical and pathologic diagnosis. METHODS: We performed a chart review of all HCT patients who died and underwent autopsy in our ICU between 2006-2016. We evaluated the presumed clinical diagnosis and confidence in the diagnosis by chart review, the pathologic diagnosis on autopsy, and whether the clinical-pathologic diagnoses were concordant. When there was discordance, we evaluated whether knowledge of the pathology could have changed management. RESULTS: Thirteen patients underwent autopsy after dying. Infection was the presumed cause in 11/13 cases. The clinical and pathologic diagnoses were concordant in 6/13(46%). In the seven discordant cases (all clinically diagnosed as infection), autopsy revealed two non-infectious inflammatory causes, one post-transplant lymphoproliferative disorder, and three non-bacterial infectious etiology. Pathologic findings may have changed management in 7/13(54%) cases. CONCLUSIONS: In a subset of HCT-recipients who died from respiratory failure, discordance was frequent between clinical and pathologic diagnoses. The risks and benefits of obtaining tissue to improve our diagnostic accuracy requires further evaluation.

Donor-Recipient Story in Allogeneic Hematopoietic Stem Cell Transplantation.

Patients with a variety of blood, immune, and metabolic disorders may require an allogeneic hematopoietic stem cell transplant as part of their treatment. However, over 70% of these patients do not have a matched sibling donor and require an alternative donor, such as a matched unrelated donor. We present a multi-part story of a Canadian stem cell recipient who underwent transplantation for treatment of refractory chronic myelogenous leukemia, and the matched unrelated donor who saved his life. The story segments feature excerpts from interviews with the donor and the recipient, along with representative images of both storytellers. The excerpts were optimized for publication on social media and were arranged to build a story arc that parallels the journey of the donor and recipient together. This donor-recipient story may serve as a resource to help raise awareness about stem cell donation and to encourage eligible individuals to register as donors. The story is one of several developed by Why We Swab, a library of stories in stem cell donation in Canada (Facebook, Twitter, and Instagram; @WhyWeSwab) to support the recruitment of committed unrelated donors.

Perspectives on Advance Care Planning for Patients with Hematologic Malignancy: An International Clinician Questionnaire.

Rationale: Critical illness is common in patients with hematologic malignancy (HM). Advance care planning (ACP) can allow these patients to express their care preferences before life-threatening illnesses. Objectives: To evaluate physicians' perspectives surrounding ACP in patients with HM. Methods: We administered a survey to intensivists and hematologic oncologists who care for patients with HM across Canada and the United Kingdom. Potential respondents were identified from institutions that have a hematologic-oncology program. The survey was disseminated electronically. Results: A total of 111 physicians completed the survey, with a response rate of 19% (39% across those who opened the e-mail); 52% of respondents were intensivists, and 48% of respondents were hematologic oncologists. Of the responses, 15.5% of physicians reported that ACP happens routinely at their institution, whereas 8.3% of physicians stated that code status is routinely discussed. ACP discussions were most commonly reported at the onset of critical illness (84.3% of respondents), during disease recurrence (52.9% of respondents), or during the transition to a strictly palliative approach (54.9% of respondents). Commonly cited barriers to ACP centered on physicians' concern about the reaction of the patient or family. Conclusions: This study emphasizes the need for earlier and more frequent ACP discussions in this high-risk population with a variety of barriers identified.

Critical illness in patients with hematologic malignancy: a population-based cohort study.

PURPOSE: To describe the modern incidence and predictors of ICU admission for adult patients newly diagnosed with a hematologic malignancy. METHODS: We conducted a population-based cohort study of adults with a new diagnosis of hematologic malignancy (April 1, 2006-March 31, 2017) in Ontario, Canada. We described the baseline demographic, clinical and laboratory predictors of ICU admission and subsequent mortality. The primary outcome was the incidence of ICU admission within 1 year of hematologic malignancy diagnosis. We assessed the predictors of ICU admission using Cox-proportional models that accounted for the competing risk of death and reported as subdistribution hazard ratios (sHR) with 95% confidence intervals (CI). RESULTS: A total of 87,965 patients (mean [SD] age, 67.8 (15.7) years) were included. The 1-year incidence of ICU admission was 13.9% (median time 35 days), ranging from 7.3% (indolent lymphoma) to 22.5% (acute myeloid leukemia). After multivariable adjustment, compared to indolent lymphoma, acute myeloid leukemia (sHR, 3.09; 95% CI 2.84-3.35), aggressive non-Hodgkin lymphoma (sHR, 2.47; 95% CI 2.31-2.65) and acute lymphoblastic leukemia (sHR, 2.46; 95% CI 2.15-2.80) had the highest risk of ICU admission. Comorbidities such as cardiovascular disease (sHR, 2.09; 95% CI 2.01-2.19), chronic obstructive pulmonary disease (sHR, 1.33; 95% CI 1.26-1.39) and baseline laboratory abnormalities (anemia, thrombocytopenia and high creatinine) were also associated with ICU admission. Among ICU patients, 36.7% required invasive mechanical ventilation and in-hospital mortality was 31%. CONCLUSION: Critical illness in patients with a newly diagnosed hematologic malignancy is frequent, occurring early after diagnosis. Certain baseline characteristics can help identify those patients at the highest risk.